Deconstructing Cell Fate Transition Dynamics and Epigenetic Heterogeneity using Single Cell Technology

The creation of pluripotent stem cells (PSCs) from any tissue through reprogramming yields induced pluripotent stem cells (iPSCs). However, reprogramming protocols are not trivial and are nearly always inefficient, often yielding an efficiency of less than 0.1%. Similar low efficiencies occur for many forward differentiation protocols, where it is also a major question which cell types are made and how they compare to cells present in vivo. In this work, single-cell RNA-sequencing was applied to iPSC reprogramming from different somatic cells to define the transcriptional changes in the process and the role of reprogramming factors and somatic transcription factors in the reorganization of cell identity, revealing the critical role of intermediate ectopic gene expression.

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